Wound dressing device

ABSTRACT

The present invention comprises methods and compositions for treating wounds. More particularly, the present invention comprises methods and compositions for wound dressing devices comprising a matrix comprising a polymer network and a non-gellable polysaccharide having active agents, such as wound healing agents, incorporated therein. The matrix may be formed into any desired shape for treatment of wounds.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 08/971,074, filed Nov. 14, 1997, now U.S. Pat. No. 5,928,174.

FIELD OF THE INVENTION

The present invention relates generally to the field of wound dressingsand particularly to compositions and methods for delivering activeagents to wounds. More particularly, the present invention relates totreatments of wounds in providing methods and compositions fordebridement of wounds and delivery of wound healing compositions.

BACKGROUND OF THE INVENTION

The outer layer of skin surrounding the body performs an importantprotective function as a barrier against infection, and serves as ameans of regulating the exchange of heat, fluid and gas between the bodyand external environment. When skin is removed or damaged by beingabraded, burned or lacerated, this protective function is diminished.Areas of damaged skin are conventionally protected by the application ofa wound dressing which facilitates wound healing by acting as a skinsubstitute.

Wounds to skin and the underlying tissues of animals may be caused byexternal insult such as friction, abrasion, laceration, burning orchemical irritation. Damage to such tissues may also result frominternal metabolic or physical dysfunction, including but not limited tobone protrudence, diabetes, circulatory insufficiencies, or inflammatoryprocesses. Normally tissue damage initiates physiological processes ofregeneration and repair. In broad terms, this process is referred to asthe wound healing process.

The wound healing process usually progresses through distinct stagesleading to the eventual closure, and restoration of the natural functionof the tissues. Injury to the skin initiates an immediate vascularresponse characterized by a transient period of vasoconstriction,followed by a more prolonged period of vasodilation. Blood componentsinfiltrate the wound site, endothelial cells are released, exposingfibrillar collagen, and platelets attach to exposed sites. As plateletsbecome activated, components are released which initiate events of theintrinsic coagulation pathway. At the same time, a complex series ofevents trigger the inflammatory pathways generating soluble mediators todirect subsequent stages of the healing process.

Normally, the wound healing process is uneventful and may occurregardless of any intervention, even in the case of acute or traumaticwounds. However, where an underlying metabolic condition or perpetualinsult such as pressure is a contributing factor, the natural woundhealing process may be retarded or completely arrested, resulting in achronic wound. Trends in modern medical practices have shown that thewound healing of both acute and chronic wounds may be significantlyimproved by clinical intervention using methods and materials thatoptimize wound conditions to support the physiological processes of theprogressive stages of wound healing. Key factors in providing theoptimal conditions are the prevention of scab formation and themaintenance of an optimal level of moisture in the wound bed. Both ofthese factors can be controlled by the management of wound exudatefluid.

A common problem in the management of both acute and chronic wounds isthe maintenance of an optimal level of moisture over the wound bedduring heavy exudate drainage. This is usually, but not always, an earlystage of healing. Most moist wound dressing technologies such as thinfilms, hydrocolloid dressings and hydrogels are typically overwhelmed bythe accumulated exudate moisture during this heavy drainage phase.Management of moisture during heavy exudate drainage often necessitatesthe use of gauze or sponge packings that wick away excess moisture fromthe wound bed, thin film coverings that trap exudate fluid over thewound bed, or calcium alginate dressings that chemically bind exudatemoisture due to the hydroscopic properties of the seaweed extract.

Examples of wound dressings that have been developed include collagendressings. Soluble collagen has been used as a subcutaneous implant forrepairing dermatological defects such as acne scars, glabellar furrows,excision scars and other soft tissue defects. Collagen has also beenused in many forms as wound dressings such as collagen sponges, asdescribed in Artandi, U.S. Pat. No. 3,157,524 and Berg et al., U.S. Pat.No. 4,320,201. However, most of these dressings are not satisfactory forthe various types of full thickness wounds. Collagen films and spongesdo not readily conform to varied wound shapes. Furthermore, somecollagen wound dressings have poor fluid absorption properties andundesirably enhance the pooling of wound fluids.

Another example of wound dressings that have been developed arehydrocolloid dressings. United Kingdom Patent Number 1,471,013 andCatania et al., U.S. Pat. No. 3,969,498 describe hydrocolloid dressingsthat are plasma soluble, form an artificial eschar with the moistelements at the wound site, and gradually dissolve to releasemedicaments. These dressings comprise a hydrophilic foam of dextranpolymer that can be applied without therapeutic agents or ointments, arenon-irritating to the lesion and can be easily removed.

Known hydrocolloid dressings in general, and the Catania et al.dressings in particular, are subject to a number of drawbacks. The majordisadvantages of these dressings include the potential to disintegratein the presence of excess fluid at the wound site, and minimal,virtually negligible, control over water loss from the wound. Thislatter disadvantage is particularly important, as excess water loss froma wound will cause an increase in heat loss from the body as a whole,potentially leading to hypermetabolism. In addition, hydrocolloiddressings require frequent dressing changes. This is especially true ofthe Catania et al. dressing due to the dissolution of the dextranpolymer at the wound site caused by the fluid loss through the wound inthe exudative stage.

Although currently available dressing materials possess features thatcontribute to the control of heavy exudate drainage, most also possesssignificant limitations that retard the overall healing process. Forexample, thin film dressings such as those described in U.S. Pat. No.3,645,835, maintain excessive moisture over the wound bed, contributingto the overhydration or maceration of surrounding skin. Although spongesand gauze support tissue, they require frequent changing, and causeirritation to the wound bed during body movement and dressing removal.Calcium alginates turn into a gelatinous mass during interaction withmoisture, are difficult to remove completely, and often dehydrate thewound bed due to the hydroscopic nature of the matrix.

Importantly, none of the presently available devices significantlycontribute to or support the autolytic debridement phase, which is thenatural removal process of necrotic tissue and debris from the wound.Autolytic debridement is a key early stage event that precedes repairphases of healing. When wound conditions are not optimal for supportingautolytic debridement, then clinical procedures such as surgicalremoval, irrigation, scrubbing, and enzymatic or chemical methods mustbe used to remove the necrotic tissue and escar that can inhibit woundhealing.

Temporary or permanent wound dressings that are designed to enhancewound healing are needed to cover large open wounds on patients withextensive burns, lacerations and skin damage. Furthermore the ability toproduce wound dressings in a variety of shapes to accommodate multiplesizes and forms of injuries is important in the manufacture of usefulmedical products.

In addition, there continues to be a need for a wound dressing thatpossesses high moisture absorption capacity, a high rate of absorption,as well as a capacity to regulate moisture at the wound bed-dressinginterface. Desirably, such a wound dressing device should stimulate theautolytic debridement process, especially during the heavy exudatingphase of wound care management.

Another desirable aspect of a wound dressing would be the ability todeliver active agents to the site of injury to accelerate wound healing.Active agents for use in wound treatment may be administered to anindividual in a variety of ways. For example, active agents may beadministered topically, sublingually, orally, or by injection(subcutaneous, intramuscular or intravenous). Nevertheless, there aredrawbacks to many of these methods, and an inexpensive, reliable,localized and relatively pain-free method of administering an activeagent has not been provided in the prior art.

One common method employed for the treatment of wounds is the topicalapplication of a salve or ointment. Yet many times, topical applicationto a wound can be painful. Additionally, in the case of a deeplycavitated wound in particular, an excess of active agent may be requiredbecause the agent must diffuse through layers of necrotic tissue andnewly forming epidermal tissues. This difficulty in delivering the agentmay require the application of an excessive amount of the agent andpreclude an accurate determination of the effective amount of activeagent to be added.

The oral and sublingual administrations of active agents used in woundtreatment also have their drawbacks. Most importantly, theadministration site, the mouth, is normally far removed from the actuallocation of the wound. Ingestion of an active agent at a site distantfrom the wound may result in the agent having negative system-wideeffects and possibly knocking out the normal flora, or normal microbialenvironment, whose presence benefits an individual. Successfulabsorption of the agent into the bloodstream also depends on severalfactors such as the agents stability in gastrointestinal fluids, the pHof the gastrointestinal tract, solubility of solid agents, intestinalmotility, and gastric emptying.

Injection of an active agent, a normally painful method ofadministration, may have the same negative system-wide effects as thatof an oral or sublingual administration if injection is at a sitedistant from the wound. Yet more importantly, a danger inherent in theinjection of an active agent is that rapid removal of the agent isimpossible once it is administered. There is also a risk of transmissionof infections and the possibility of vascular injury due to the use ofneedles.

Therefore, topical, oral, sublingual and intravenous methods ofadministration pose several problems when delivering active agents forthe treatment of wounds. What is needed is a method of administering anactive agent for the treatment of wounds in an effective, safe andrelatively pain-free manner.

SUMMARY OF THE INVENTION

The present invention comprises compositions and methods for thetreatment of wounds. In particular, the present invention providesmethods and compositions for administering active agents to the site ofa wound via wound dressings with active agents incorporated therein. Thepresent invention also allows for localized delivery of active agentsand prevents the negative effects of system wide administration. Thepresent invention comprises wound healing devices that have specializedstructures that aid in treatment of wounds.

In a preferred embodiment of the present invention, active agents areincorporated directly into micro-cavities of the matrix of the wounddressing devices. The agents may be incorporated by absorption of agentsby the matrix, and preferably by incorporation during the polymerizationof the matrix. It is theorized that the release of the active agents maybe controlled via manipulation of concentration parameters, movement ofwater through the matrix and the degree of cross linking in the matrix.In a further preferred embodiment, the wound dressings comprise astranded configuration, wherein the strands extend from at least onecommon region and the strands themselves comprise a polymer matrix.

The wound dressing devices of the present invention may be used tosimultaneously deliver a number of active agents to a wound site. Woundhealing agents such as antimicrobial agents, antifungal agents,antiviral agents, growth factors, angiogenic factors, anaesthetics,mucopolysaccharides and other wound healing proteins may be incorporatedinto the wound dressings for controlled release. Adjuvants and otheragents, such as those that boost the immune system, may also beincorporated into the wound dressings devices of the present invention.A surprising and novel aspect of the preferred embodiment having agentsdirectly incorporated into micro-cavities of the matrix is that theactivities of the wound healing agents are not altered by incorporationinto the devices and that the agents are effective upon their release.

In a preferred embodiment of the present invention, the wound dressingdevices of the present invention comprise a novel stranded structuremade from a matrix suitable for application to broken skin andunderlying tissues. The individual strands of the preferred embodimentmay or may not have free floating ends, however, the unique arrangementof the device allows it to both absorb excess wound exudate, andsimultaneously conform closely to the walls of the wound bed, in orderto accelerate overall wound healing.

The preferred stranded configuration of the present invention isparticularly desirable because the novel design provides a high surfacearea to volume ratio to maximize interchange between the matrix andwound moisture and wound debris. The multiple strands of the preferredconfiguration provide maximal inter-strand space to serve as a reservoirfor moisture, necrotic materials, or agents scheduled for delivery tothe wound bed. The superior moisture absorption and regulation capacityof the preferred embodiment equip the wound dressing devices for use onheavily to moderately draining wounds.

In addition to increased moisture absorption and the ability to deliveractive agents, the individual strands of the preferred configuration mayparticipate in mechanical debridement thereby accelerating the woundhealing process. The individual strands of the preferred wound dressingsincrease the inherent flexibility of the device, and enhanceconformability to the irregularities of the contours in the woundcavity, allowing the preferred devices to be used in deeply cavitatedwounds where debridement is essential. In order to simplify the overallwound dressing procedure, the preferred devices may have a single unitconstruction that is applied and removed as a complete unit, leaving noremnants. Additionally, the preferred devices may be left in place forprolonged periods between changes.

Accordingly, it is an object of the present invention to providecompositions and methods for the treatment of wounds.

Another object of the present invention is to provide compositions andmethods that facilitate and accelerate the wound healing process.

Yet another object of the present invention is to provide a wounddressing device wherein active agents are incorporated.

It is another object of the present invention to provide wound dressingdevices that absorb excess moisture at a wound site.

It is another object of the present invention to provide wound dressingdevices that promote autolytic debridement.

Yet another object of the present invention is to provide a wounddressing device that absorbs wound exudate by allowing for optimalcontact between the device and the wound area.

A further object of the present invention is to provide wound dressingdevices for external and internal wounds.

Another object of the present invention is to prevent infection byproviding wound dressing devices that clean wound sites by removingdebris and contaminating material.

It is another object of the present invention to provide wound dressingdevices that easily conform to the shape of a wound.

It is yet another object of the present invention to provide wounddressing devices that are easily manufactured.

Still another object of the present invention is to provide wounddressing devices that may be easily removed from wounds and replaced.

Yet another object of the present invention is to provide wound dressingdevices that are compatible with injured tissue and do not induceirritation or inflammation.

It is yet another object of the present invention to provide wounddressing devices that function to both absorb wound exudate and promoteautolytic debridement.

Another object of the present invention is to provide methods andcompositions for making single unit construction wound dressing deviceshaving multiple strands.

It is another object of the present invention to provide methods andcompositions for treating wounds using wound dressing devices thatfunction to both absorb wound exudate and deliver wound healing agents.

An object of the present invention to provide methods and compositionsfor treating wounds using wound dressing devices having active agentsincorporated therein.

Still another object of the present invention is to provide methods andcompositions for delivering active agents to wound sites and damagedtissue.

These and other objects, features and advantages of the presentinvention will become apparent after a review of the following detaileddescription of the disclosed embodiments and the appended claims.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a three dimensional view of one embodiment of a wound dressingdevice of the present invention wherein the multi-stranded device mayhave free floating strand ends.

FIG. 2 presents a cross-section of a strand of the multi-strand device.

FIG. 3 is an illustration of a pattern of a die used for cutting adevice from an appropriate matrix material.

FIGS. 4-7 illustrate additional embodiments of a wound dressing device.

DETAILED DESCRIPTION

The present invention comprises compositions and methods for thetreatment of wounds. In particular, the present invention comprisescompositions and methods for treating wounds using wound dressingdevices with active agents incorporated therein. In a preferredembodiment, the active agents may be directly incorporated into thematrix of the devices for controlled release at the site of the wound.In a further preferred embodiment, the matrix comprises a polymernetwork with a non-gellable polysaccharide dispersed evenly throughoutsaid network. The matrices of this preferred embodiment provide areliable and efficient means for delivering active agents to the woundwhile at the same time provide a superior moisture regulation capacityfor promoting wound healing.

The wound dressing devices of the present invention may also take aparticular conformation. For example, a preferred embodiment of thepresent invention comprises a stranded configuration wherein theindividual strands extend from at least one common region and may havefree floating ends. This particular conformation is particularlysuitable for use in deeply cavitated wounds since the multiple matrixstrands enable the dressing to conform to individual and uniquely shapedwound areas. Furthermore, the devices accelerate wound healing bydisplacing and allowing for the removal of excess cellular exudate anddebris, thereby improving the rate of tissue repair and regeneration.

Definitions

The terms “a”, “an” and “the” as used herein are defined to mean one ormore and include the plural unless the context is inappropriate.

Active agents

The active agents incorporated into the wound dressing devices of thepresent invention may be used for the treatment of wounds or in skinhealing. The active agents may participate in, and improve, the woundhealing process, and may include antimicrobial agents, including but notlimited to antifungal agents, antibacterial agents, anti-viral agentsand antiparasitic agents, growth factors, angiogenic factors,anaesthetics, mucopolysaccharides, metals and other wound healingagents.

Examples of antimicrobial agents that can be used in the presentinvention include, but are not limited to, isoniazid, ethambutol,pyrazinamide, streptomycin, clofazimine, rifabutin, fluoroquinolones,ofloxacin, sparfloxacin, rifampin, azithromycin, clarithromycin,dapsone, tetracycline, erythromycin, ciprofloxacin, doxycycline,ampicillin, amphotericin B, ketoconazole, fluconazole, pyrimethamine,sulfadiazine, clindamycin, lincomycin, pentamidine, atovaquone,paromomycin, diclazaril, acyclovir, trifluorouridine, foscarnet,penicillin, gentamicin, ganciclovir, iatroconazole, miconazole,Zn-pyrithione, and silver salts such as chloride, bromide, iodide andperiodate.

Growth factor agents that may be incorporated into the wound dressingdevices of the present invention include, but are not limited to, basicfibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF),nerve growth factor (NGF), epidermal growth factor (EGF), insulin-likegrowth factors 1 and 2, (IGF-1 and IGF-2), platelet derived growthfactor (PDGF), tumor angiogenesis factor (TAF), vascular endothelialgrowth factor (VEGF), corticotropin releasing factor (CRF), transforminggrowth factors α and β (TGF-α and TGF-β), interleukin-8 (IL-8);granulocyte-macrophage colony stimulating factor (GM-CSF); theinterleukins, and the interferons.

Other agents that may be incorporated into the wound dressing devices ofthe present invention are acid mucopolysaccharides including, but arenot limited to, heparin, heparin sulfate, heparinoids, dermatan sulfate,pentosan polysulfate, chondroitin sulfate, hyaluronic acid, cellulose,agarose, chitin, dextran, carrageenin, linoleic acid, and allantoin.

Proteins that may be especially useful in the treatment of woundsinclude, but are not limited to, collagen, cross-linked collagen,fibronectin, laminin, elastin, and cross-linked elastin or combinationsand fragments thereof. Adjuvants, or compositions that boost an immuneresponse, may also be used in conjunction with the wound dressingdevices of the present invention.

Other wound healing agents that are contemplated in the presentinvention include, but are not limited to, metals. Metals such as zincand silver have long been known to provide excellent treatment forwounds. Delivery of such agents, by the methods and compositions of thepresent invention, provide a new dimension of care for wounds.

It is to be understood that in a preferred embodiment of the presentinvention, the active agents are incorporated into the wound dressingdevices so that the agents are released directly from the devices andfurther delivered via transdermal or transmucosal pathways. Theincorporated agents may be released over a period of time, and in thisway, the devices retain their ability to kill or inhibit microorganismsor boost the body's immune response over an extended period of time inorder to facilitate wound healing.

Administering active agents for the treatment of wounds by using thewound dressing itself overcomes several of the problems of the priorart. First, the present invention avoids the painful re-application ofsalves and ointments to the wound. The present invention also allowsactive agents to be delivered directly into the site of the wound toprevent the negative impact of system wide delivery of the agents asencountered after oral or intravenous administration. In the case ofdeeply cavitated wounds, in contrast to the topical application ofactive agents, the wound dressing and active agents therein may belocated directly within the wound, providing a more effective deliveryof the agents. Finally, in contrast to an injection of active agents,the present invention provides methods of administering active agentswherein the agents may be removed immediately from the wound and theadministration terminated.

Matrices

The wound dressing devices of the present invention comprise a matrixmaterial, and most preferably, having one or more active agents areincorporated therein. In a preferred embodiment of the presentinvention, the matrix is flexible and elastic, and is a semi-solidscaffold that is permeable to substances such as inorganic salts,aqueous fluids and dissolved gaseous agents including oxygen. Thesubstances permeate the matrix through movement via intermolecularspaces among the cross-linked polymer.

Preferably, the matrix material is constructed from a natural orsynthetic polymer and a non-gellable polysaccharide. Natural polymersthat may be used for the construction of the wound device include, butare not limited to collagen, animal hide, hyaluronic acid, dextran andalginate. Synthetic polymers that may be used include, but are notlimited to polyacrylamide, polyacrylate, polybuterate, polyurethanefoam, silicone elastomer, rubber, nylon, vinyl or cross linked dextran.If cross-linked dextran is used, it is preferred that the molecularweight of the dextran polymer is between 50,000 and 500,000. The mostpreferable non-gellable polysaccharide is a non-gellable galactomannanmacromolecule such a guar gum. A range of guar gum between approximately0.01 kg to 100 kg, preferably between approximately 0.1 kg to 10 kg, andmost preferably between approximately 0.5 kg to 2 kg is generallysufficient. Other non-gellable polysaccharides may include lucerne,fenugreek, honey locust bean gum, white clover bean gum and carob locustbean gum.

To decrease the permeability of wound dressing devices comprising across-linked polymer and non-gellable polysaccharide matrix, water losscontrol agents may be applied to the surface of the device. Applicationof water loss control agents is preferred since a decrease in thepermeability of the device controls the loss of fluids from the wound.The preferred water loss control agent is petrolatum, however, otherwater loss control agents such as glycolipids, ceramides, free fattyacids, cholesterol, triglycerides, sterylesters, cholesteryl sulfate,linoleic ethyl ester and silicone oil may also be used.

If desired, a plasticizer may also be added to the matrix material. Thepresently preferred plasticizer is glycerol and water, however,propylene glycol and butanol may also be used. If glycerol is used, arange of between approximately 0.5 kg to 50 kg, preferably between 1 kgand 30 kg, and most preferably between approximately 5 kg to 15 kg isgenerally sufficient. The plasticizer may be added in the initialmixture of polymer and cross-linking agent.

If desired, a hydration control agent may be incorporated into thematrix. The preferred hydration control agent is an isopropyl alcohol,however, ethanol, glycerol, butanol, and propylene glycol may also beused. A range of isopropyl alcohol of between approximately 0.1 kg to 10kg, preferably between approximately 0.2 kg to 5 kg and most preferablybetween approximately 0.5 kg to 2 kg is generally sufficient.

The matrix of the preferred embodiment preferably comprises polymerizedchains of acrylamide monomer, wherein the acrylamide monomers arecross-linked with a cross-linking agent, a non-gellable polysaccharide,and an active agent or pharmaceutical directly encapsulated intomicro-cavities therein. A range of acrylamide between approximately 1 kgto 100 kg, preferably between approximately 2 to 50 kg, and mostpreferably between approximately 5 kg to 20 kg is generally sufficient.

The most preferable cross-linking agent is NNNN′-methylenebisacrylamide,however other appropriate cross-linking agents such asbisacrylylycystamine and diallyltartar diamide may also be used. IfNNNN′-methylenebisacrylamide is used, a range of between approximately0.01 kg to 1 kg, preferably between approximately 0.02 kg to 0.5 kg, andmost preferably between approximately 0.05 kg to 0.3 kg is generallysufficient. As noted above, the most preferable non-gellablepolysaccharide is a non-gellable galactomannan macromolecule such a guargum, but other non-gellable polysaccharides may include lucerne,fenugreek, honey locust bean gum, white clover bean gum and carob locustbean gum.

Ammonium persulfate and TEMED may also be added to the matrix. A rangeof ammonium persulfate between approximately 0.01 kg to 1 kg, preferablybetween approximately 0.02 kg to 0.5 kg, and most preferably betweenapproximately 0.05 kg to 0.2 kg is generally sufficient. Additionally, arange of TEMED between approximately 0.01 kg to 1 kg, preferably betweenapproximately 0.02 kg and 0.5 kg, and most preferably betweenapproximately 0.05 kg to 0.3 kg is generally sufficient.

Incorporation of active agents

One embodiment of the matrices of the present invention can be found inU.S. Pat. No. 5,196,190 to Nangia et al., which is hereby incorporatedin its entirety. Nangia et al. teach a matrix composed of a natural orsynthetic polymer, a non-gellable polysaccharide, and a phospholipidbased drug delivery system. In particular, Nangia et al. teach a matrixcapable of drug delivery, wherein lipid vesicle liposomes containing adesired drug are incorporated into the matrix.

One problem with the prior art methods, however, is the difficulty ofincorporating active agents into the liposomes since some agents may beincompatible with liposome chemistry. Incorporation using liposomes istime consuming, expensive and sometimes unreliable because dispersion ofthe liposomes in the matrix is difficult to achieve and once achieved,the liposomes may prematurely release costly agents due the liposomes'inherent instability. Another problem is that the prior art fails toteach a method of incorporating active agents into a wound dressingwherein the release of the agent over time can be controlled through themanipulation of concentration parameters, movement of water through thematrix and the degree of cross linking in the matrix.

Preferred embodiments of the present invention however, address the needfor a less expensive, quicker, and more reliable method forincorporating a wider range of desired agents into wound dressingdevices. Preferred embodiments also provide a means to control therelease of the desired agents over time via manipulation ofconcentration parameters, movement of water through the matrix and thedegree of cross-linking in the matrix. In a preferred embodiment, thedesired agents may be directly incorporated into the matrix by addingthe agents into the initial formulation for the matrix prior tocross-linking. This method of incorporation is inexpensive, rapid andreliable, and most surprisingly, the incorporated agents are notaffected by the process of polymerization and retain their biologicalactivities.

Using preferred embodiments of the present invention, delivery of thedesired agents may be controlled by the use of movement of liquidthrough the matrix. Though not wishing to be bound by any theory, it istheorized that the liquid in a matrix of polymer and non-gellablepolysaccharide is either bound to the non-gellable polysaccharide or itis unbound in the polymer mass. Thus, it is theorized that the presentinvention uses the free liquid portion of the matrix as a generalsolvent and as a means to deliver desired agents. Soluble drugs areeasily dissolved in the free liquid portion, however slightly solubledrugs are ground to a fine powder and may require the use of a wettingagent such as glycerol or isopropyl alcohol or a surfactant such aspolysorbate, triton-X or sodium lauryl sulfate.

Once the desired active agent or agents are dispersed throughout thematrix, a portion of the agent resides in the non-gellablepolysaccharide, while another portion of the agent is dissolved in thefree liquid phase and moves freely through the matrix. The ability ofthe agent to move freely throughout the matrix in the free liquid phaseis important in the agent delivery system of the present invention.Because the agent is dissolved in the free liquid phase, a concentrationgradient of the active agent is created between the matrix of a wounddressing device and the moisture of the wound itself. Therefore, whenthe matrix is placed onto a moist surface such as an open wound, thesoluble agent will move through the free liquid phase toward theagent-free wound moisture, resulting in the delivery of the agent to thewound. This movement of soluble agent further upsets the equilibriumbetween soluble and insoluble agents, and causes more agent to dissolveinto the free liquid phase, thus causing more agent to be delivered tothe wound. Because the present invention incorporates the desired agentdirectly into the matrix rather than incorporating the drug into otherdelivery vehicles, such as liposomes, the agent may be dissolved in thefree liquid phase and reliably delivered to the wound through theprocess described above.

Delivery of the desired agents may also be controlled by the degree ofcross-linking in the matrix. As described above, the desired agents maybe added to the other ingredients forming the matrix prior to theaddition of the cross-linking agent. Subsequent addition of the crosslinking agent and concomitant polymerization results in both chainelongation of monomeric chemicals and cross-linking between chains ofmonomers. The combination of chains cross-linked together createsmicro-cavities wherein the desired agents are encapsulated. Bycontrolling the amount of cross-linking agent and the length of chainsof monomer, it is possible to regulate the size of the micro-cavities inthe polymer. Larger micro-cavities, produced by a lower degree ofcross-linking, allow for freer migration and quicker delivery of thedesired agent, whereas smaller micro-cavities increase the deliverytime. Although the liposome based delivery system may also make use ofthe degree of cross-linking, the liposome itself acts as an additionalbarrier to delivery, making delivery less controlled and less reliable.

Stranded structure

The wound dressing devices of the present invention may take manyphysical forms, however, preferred embodiments are primarily constructedof thin strands of matrix suitable for placement into the wound bed orcavity. The preferred devices may be constructed from one or multiplestrands of matrix. When multiple strands are used in the construction,the strands are secured together by wrap, tie, glue, or alternatively bya continuous bridge of matrix between adjacent strands. Multiple strandsare secured together to minimize accidental loss during removal of thedressing from the wound bed. Typically, the strands of particularembodiments are bound or secured in the mid-region so that the ends ofthe device may float free. The advantage of free floating strands is toenable the individual strands to access a maximum volume of the woundand thereby absorb the excess fluid, exudate and debris. The mechanicalaction of the free floating strands contributes to the trapping andremoval of cellular and wound debris. Concurrently the free floatingstrands also conform optimally with the contours of the wound surface tomaximize contact between the device and the wound bed.

Referring now to the drawings, one preferred conformation of the wounddressing devices of the present invention is now described. Thispreferred conformation is useful for the control of exudate moistureaccumulation, for stimulation of mechanical and autolytic debridement,and for delivery of active agents.

FIG. 1 is a three dimensional view of a preferred embodiment of thewound dressing device 10 with a strand 20 of the multi-strand devicewith free floating strand ends 40. The strands are secured together by abridge 30 created during the cutting stage and composed of the matrixmaterial used to construct the device. FIG. 2 represents a cross-section22 of a strand 20 of the multi-strand device 10. It is intended that thecross-section 22 illustrate the sum of the linear dimensions of thesides. Preferably the sum of the linear dimensions of the sides is atleast twice the numerical value of the surface area of the cross-sectionto provide an adequate surface area to volume ratio of the strands. Morepreferably, the sum of the linear dimensions of the sides is four ormore times the numerical value of the surface area of the cross section.

FIG. 3 is an illustration of the pattern of a die 45 used for cutting apreferred embodiment of the wound dressing device 10 from an appropriatematrix material. Cutting blades 55, around the perimeter of the die,release the cut-out from the stock sheet of matrix during the cuttingphase of production. Within the perimeter, a series of cutting blades 57are situated lying parallel to one another extending from the ends ofthe pattern toward the center but not continuing through the center soas to leave a region 50 of uncut material in the center. The pattern ofblades may vary according to the purpose of the wound dressing device.For example, the patterns may vary in terms of numbers of strands 20,numbers of regions of uncut region 50 for bridging strands, and thepositioning of the single or multiple bridges 50 relative to the ends ofthe strands. The cross section 22 of the strands may be any suitabledimension that allows the appropriate interaction between strands andwound environment. The matrix may be any non-dissolving material that issuitable for contacting the broken skin, and underlying tissuesincluding non-absorbent natural or synthetic materials, or absorbentnatural or synthetic materials.

FIG. 4 illustrates a pattern that is an alternative embodiment. It is acircular pattern for making an embodiment 80 whereby the strands 90radiate away from a central region of uncut matrix that joins theadjacent strands in the unit. FIG. 5 illustrates a pattern for making anembodiment whereby the bridge 95 of matrix is offset to one end of thepattern enabling the strands 100 to radiate away from the bridge in asingle direction. FIG. 6 illustrates a pattern for making an embodimentwhereby the strands 120 are irregular in shape over their length fromthe matrix bridge 100. FIG. 7 illustrates a pattern for making anembodiment whereby the strands are conjoined at several bridges alongthe length of the device and at the ends of the device. It is to beunderstood that the pattern can be any variation of these embodimentsand is still within the scope of the present invention.

The unique stranded embodiment is particularly desirable because itenables the device to maintain its integrity and also maximize thesurface area to volume ratio of its matrix. This is important since thematrix may be an absorbent material where a high surface area to volumeratio increases the rate of absorption, without increasing the overallabsorption capacity of the device.

In a preferred embodiment, the wound dressing is principally constructedof a “stranded” matrix, which allows for optimal contact between thestrands and the wound area. In addition, the stranded matrixconstruction maximizes the overall flexibility and pliability of thedressing. In embodiments of the device where multiple strands areemployed, the overall flexibility and conformational characteristics ofthe device are maintained by binding strands in only limited andrestricted areas. Minimal binding of the strands prevents the formationof rigid areas and allows for the effective and optimal utilization ofnumerous strands in a single device without adversely diminishingcontact with the surface of the wound bed.

Another advantage of the stranded matrix construction is the“semi-porous” quality of the wound dressing that allows for the removalof extraneous cellular matter resulting during the wound healingprocess. The air in the inter-strands area of the device serve as areservoir of space that may be displaced allowing for the removal ofexcess materials such as exudate fluid, debridement product and cellularexudate from the wound bed. As this region fills, the device may swellto provide “support” to the wound bed and surrounding tissues. A woundconstitutes damaged or “missing” tissue, and when tissue is missing, thesurrounding tissue may “collapse” or sag into the void. “Support” inthis context therefore, means the temporary filling of the void to holdthe surrounding tissue in place where it should reside.

Removal of debridement product and cellular exudate is furtherfacilitated by unbound, loose strands of the wound dressing devices.When placed upon a wound, the loose strands of the devices randomlyorient in the wound bed where the thin filamentous strands and freefloating ends contribute to mechanical debridement of necrotic slough.Since the strands are secured and bound in at least one region, amechanical union is formed, ensuring that all strands and necrotictissue accumulation in the inter-strand spaces are removed from thewound when the device is changed. By contributing to the removal ofextraneous wound products and cellular debris, the wound dressing devicepermits cleaning of the wound which in turn prevents and decreases thepossibility of infection and contamination.

In one embodiment, the wound dressing device is constructed from amatrix composed of an absorbent synthetic polyacrylate material. Therate of absorption of polyacrylate is significantly increased by cuttingthe material into strands, which increases the surface area to volumeratio. Polyacrylate material is particularly suitable for the wounddressings of the present invention because it retains its integrityduring interaction with wound exudate moisture, as well as with necrotictissue and wound debris. The wound dressing device of the presentinvention does not dissolve, gel or otherwise disintegrate duringapplication to the wound. The preferred matrix swells slightly duringthe absorption of moisture, causing the device to conform closely to thewalls of the wound bed.

In a preferred embodiment, the polyacrylate matrix is cut intofree-floating strands bound together through a matrix-bridge in themid-region. This pattern of construction imparts a significantly highsurface area to volume ratio for rapid moisture movement within theabsorbent matrix.

Wound dressing devices of the present invention may be produced bycutting a desired design pattern from stock sheets of matrix material.For example, the material may be die-cut from stock sheets of anabsorbent polyacrylate wound dressing material. The stranded cut-out maythen be coated with an agent to prevent aggregation and tangling of thefree floating strands. Coating agents that may be used include, but arenot limited to, petrolatum, talcum, polyglycols, glycerol, propylene,glycol, vegetable oil, and animal oil. Following the steps of cuttingand coating, the material may be sterilized using sterilizationtechniques known in the art such as gamma radiation, steam and heatsterilization, electron beam or chemical sterilization (such as by useof ethylene oxide).

A preferred composition of the present invention comprises a matrixcomprising a polymer, a non-gellable polysaccharide, and one or moreactive agents incorporated therein. A more preferred matrix comprises anacrylamide polymer, guar gum, and one or more active agents incorporatedtherein. A most preferred matrix comprises an acrylamide polymer, guargum, has one or more active agents incorporated therein, and is formedinto a stranded structure wherein the strands are secured by at leastone common region.

The wound dressing devices of the present invention may be used oninjured tissue and for bodily fluid drainages where control andmanagement of fluid and secretions is desired. The term “bodily fluid,”as used herein, includes, but is not limited to, saliva, gingivalsecretions, cerebrospinal fluid, gastrointestinal fluid, mucous,urogenital secretions, synovial fluid, blood, serum, plasma, urine,cystic fluid, lymph fluid, ascites, pleural effusion, interstitialfluid, intracellular fluid, ocular fluids, seminal fluid, mammarysecretions, vitreal fluid, and nasal secretions.

In particular, the wound dressing devices of the preferred embodimentsare especially applicable for usage on heavily exudating acute andchronic wounds for controlling accumulating exudate moisture, support ofthe wound bed and surrounding tissues. Importantly, the wound dressingsare particularly effective for stimulating and supporting autolyticdebridement, and therefore accelerating the wound healing process.

In use, the wound dressing devices of the present invention are theprimary dressing placed in direct contact with the wound bed, or as nearas practical against the wound bed. The devices may serve as a packingmaterial and, if required, may be secured into position with anysuitable secondary wound dressing such as a wrap, tape, gauze, or pad.The dressings are temporary, however, and are not intended for permanentincorporation into the healed tissues. When necessary, the wounddressing devices are changed by first removing any over-dressingmaterial and then removing the device, whereby any accumulated necrotictissue and exudate is lifted away. The wound dressing devices of thepresent invention may be replaced by a fresh device or other suitablewound covering.

The devices may be placed in their entirety into a wound, placed incombination with additional bundles of the same design into the wound,or cut through the bridge between strands to reduce the size or numberof strands present in the wound.

The devices of the present invention may be cut, shaped and modified toaccommodate numerous uses and applications. For example, the devices maybe used as a gastric retrievable device, wherein a retrieval cord isattached to the device that is then swallowed. After absorption hastaken place, the devices may be retrieved and analyzed for content.

The devices may undergo a swelling action as they absorbs exudatemoisture, however, they will not dissolve or disintegrate. The swellingaction displaces necrotic material from the wound surface and forces thematerial into the inter-strands regions of the device. The ladenmoisture content and the retention of moisture near the wound bed by theinvention contributes to stimulation of the autolytic debridementprocess whereby the body's own enzymes break-up necrotic tissue andcellular debris. Complete removal of the device occurs due to theconjoined nature of the device.

The foregoing description includes the best presently contemplated modeof carrying out the invention. This description is made for the purposeof illustrating the general principles of the inventions and should notbe taken in a limiting sense. This invention is further illustrated bythe following examples, which are not to be construed in any way asimposing limitations upon the scope thereof. On the contrary, it is tobe clearly understood that resort may be had to various otherembodiments, modifications, and equivalents thereof, which, afterreading the description herein, may suggest themselves to those skilledin the art without departing from the spirit of the present invention.

EXAMPLE 1 Formation of a Matrix Including Acrylamide

A mixing tank was charged with 161.4 kg of water and 9.1894 kg ofacrylamide, 0.10347 kg of NNNN′-methylenebisacrylamide, and 9.3046 kg ofglycerol were added and mixed. Then 1.0213 kg of guar gum non-gellablepolysaccharide was dispersed in a mixture containing 0.9770 kg ofisopropyl alcohol and 2 kg of water. The solution of guar gum was thenadded and dispersed into the acrylamide mixture. After suitable mixing,0.1042 kg of TEMED was added and polymerization was catalyzed with0.0999 kg ammonium persulphate.

While the batch was still liquid, it was poured into molds to formsheets. After gelling had occurred, sheets were transferred to adessicator and dehydrated to form a stable intermediate stock sheet.Prior to cutting to size, the stock material was re-hydrated in a humidatmosphere. After cutting, the material was coated with petrolatum. Theresulting wound dressing device was then sealed into appropriatepackaging and irradiated to sterilize it.

EXAMPLE 2 Absorption Capacity of Polyacrylamide Matrix

It was determined that a preferred matrix material composed ofcross-linked polyacrylamide and embedded natural vegetable gum absorbedapproximately seven times its weight in water. Saturation of a flatsheet of matrix material with a thickness of 0.9 mm was achieved inapproximately 22 hours of continuous exposure to excess water. Asimilarly sized piece of flat matrix material was cut into thin strandswith a calculated 200% increase in overall surface area. The total waterabsorption of this material was also approximately seven times itsweight. However this material achieved saturation in approximately fivehours. Similar comparisons were made between an intact matrix and amatrix cut in such a way as to increase the surface area between 150%and 300%. These studies revealed that the matrices retained theiroverall absorption capacity but there was an increased rate ofabsorption proportional to the increase in surface area.

EXAMPLE 3 Matrix Absorption Capacities for Various Natural Substances

Matrices, cut into strands, were tested for absorption capacities on avariety of natural aqueous based viscous fluids. These fluids includedwater containing salt (0.15M salinity), cow's whole milk, egg whitesfrom chicken eggs, yogurt, and fetal bovine serum. The absorption ofmoisture by the test matrix strands ranged between 3.2 and 7.3 times theoriginal weight of the tested devices.

EXAMPLE 4 Absorption Capacity of Matrix in Heterogeneous BiologicalFluid

A polyacrylamide matrix of a preferred device was placed into a testtube containing fetal bovine serum, in an amount equal to five times theweight of the matrix. The matrix absorbed the aqueous fluid from theserum, leaving a concentrate of serum proteins in approximately fourhours at 4° C. The concentrated serum proteins were predominatelylocated between the strands of the device as a thick viscouscoagulation. When the device was removed from the tube, the concentratedproteins were also removed. This experiment showed that the design wouldassist in the debridement of the wound.

EXAMPLE 5 Construction of Stranded Matrices

Initial prototypes of the stranded matrices were prepared by taking flatsheets of polyacrylamide matrix and cutting them into thin strands usinga sharp instrument such as a box knife. Several methods were tested todetermine a satisfactory method for commercial production of the device.The following tests were carried out with success:

Test 5(a). Matrix material was processed through a pasta cutter using ablade for noodles.

Test 5(b). A steel rule die was constructed such that parallel bands ofsteel rules, separated by spacers were locked into a die block. Matrixwas cut by placing the die over the matrix and press-cutting with ahydraulic press.

Test 5(c). Matrix formula was compounded and catalyzed to initiatepolymerization. The matrix was then placed into a 50 ml syringe andextruded as a thin strand onto a sheet. The thin strands were allowed tocomplete polymerization and then were dried and cut to uniform lengthsfor use in the device.

Test 5(d). A rotary die was constructed with a preferred pattern. Therotary die was placed into the rotary die assembly and matrix was fedthrough between the rotary die and the anvil for cutting.

EXAMPLE 6 Optimization of Matrix Construction Utility

Several prototypes were constructed to optimize the utility of thedevice as follows:

Test 6(a) Individual strands cut from a sheet of matrix were bandedtogether using a silicone elastimer ring. The ring, having an internaldiameter of approximately 3 mm and a length of 1.5 mm, was stretchedopen so that between five to seven strands could be threaded through andsecured by the band about the middle. When placed into fluid forabsorption studies, it was found that the unit nature of the device wasretained throughout the absorption period and that the whole device wasremoved without leaving remnants in the absorption chamber.

Test 6(b) Prototypes constructed by using one strand to tie otherstrands together performed satisfactorily in absorption and retrievalstudies.

Test 6(c) Prototypes constructed by maintaining a continuous bridge ofmatrix between adjacent strands were tested and shown to performsatisfactorily in absorption and retrieval studies.

EXAMPLE 7 Incorporation of Penicillin G into the Matrix

The incorporation of the antimicrobial agent, penicillin G, into thematrix was evaluated by dissolving 1×10⁶ units of penicillin G powderinto 50 milliliters of water. Acrylamide, methylenebisacrylamide,glycerol, and a guar gum/isopropyl alcohol mixture were added to a flaskcontaining 900 ml water and mixed for two hours. The penicillin solutionwas then added to the flask along with TEMED dissolved in 25 ml water.After thorough mixing, ammonium persulphate in 25 ml water was added andmixed thoroughly. The mixture was then poured into sheet molds andallowed to gel. The sheets of semi-solid gel material were stripped fromthe mold and dehydrated to approximately 7% their original water contentfor storage. Prior to testing, the sheets were placed in a humidifiedenvironment until the sheet weight had increased to approximately118-122% the storage weight. Discs of 0.7 cm diameter were cut from thesheets. The discs were placed onto the surfaces of agar plates that hadpreviously been seeded with various strains of microorganisms (Staphaureus; E. coli; Candida albicans; Ps aeruginosa). The plates wereincubated and then examined for zones of inhibition around the discscontaining antibiotic verses control discs. Zones of inhibition weremeasured around the penicillin containing matrix but not the controlmatrix on the Staph aureas, E coli, and Pseudomonas aeruginosa plates.No zone was measured on the Candida albicans plate. These resultsdemonstrate the release of active penicillin G after its incorporationinto the matrix.

EXAMPLE 8 Incorporation of Silver Chloride Precipitate into the Matrix

Silver chloride is a weakly soluble salt that dissociates in water torelease the silver ion that may have antimicrobial activity. Silvernitrate was dissolved into the batch mixture of pre-polymerized matrixat a concentration of 5×10⁻³M and then mixed well. The silver wasprecipitated by the addition of sodium chloride to produce a colloidalsuspension of the weakly soluble salt. The batch was then polymerized bythe addition of TEMED and ammonium persulphate and cast into sheets. Thesheets were dehydrated to approximately 5% of the original moisturecontent and stored in the dark. Before testing, the sheet stock washydrated to 118-122% its storage weight and then cut into 0.7 cm discsthat were placed on the surface of pre-inoculated agar culture plates.The plates were incubated and then evaluated for growth around thediscs.

Zones of inhibition were measured around discs on plates inoculated withStaph aureus; E. coli; Candida albicans; Pseudomonas aeruginosa,indicating the release of active silver ions after incorporation intothe matrix. Hydrated sheets exposed to continuous light turned from anamber color to a uniform tan to brown color which illustrated uniformdispersion of the silver chloride precipitate.

EXAMPLE 9 Synergistic Action Between Therapeutic Agent and Adjuvant

The antifungal agent Zn-pyrithione is an active agent against a widerange of pathogenic fungi but it poorly penetrates heavily keratinizedtissues such as finger and toe nails. Matrix material containingZn-pyrithione and the keratinolytic agents salicylic acid and urea weretested for increased efficacy of delivering agents to control fungalgrowth in nail tissue. To the pre-polymerized batch material was addedsufficient Zn-pyrithione, salicylic acid and urea to give finalconcentrations of 0.01%, 5% and 5%, respectively. The batch wasneutralized to pH 6.5 by the addition of sodium hydroxide. Afterthorough mixing, the batch was poured into molds to cast into sheets.After gelling, the sheets were dehydrated to 5% the original moisturecontent and stored. Before testing, the sheet stock was hydrated to118-122% its storage weight and then cut into 0.7 cm discs which wereplaced on the surface of bovine hoof material cut thinly to resemblefinger nail. These were then transferred onto pre-inoculated agarculture plates. The plates were incubated and evaluated for growtharound the discs.

Zones of inhibition were measured around the discs on plates inoculatedwith Candida albicans. No zones were measured where Zn-pyrithione or thekeratinolytic agents were not included in the matrix. Smaller zones weremeasured where only urea and Zn-pyrithione were added. Zones ofinhibition were however measured around sets that contained both theactive agent and the keratinolytic agents in combination. These resultsdemonstrate that therapeutic agents and adjuvants may be incorporatedinto the matrix and later released in active form such that they worksynergistically.

EXAMPLE 10 Bovine Protein Incorporation into and Delivery from theMatrix

Bovine serum albumin (approximately 65,000 Daltons) and bovine gammaglobulin (approximately 155,000 Daltons) were dissolved at aconcentration of 0.1% w/w into a pre-polymerized matrix batch materialand thoroughly mixed. The batch was polymerized by the addition of TEMEDand ammonium persulphate, poured into molds and gelled into sheets. Thesheets were dehydrated to approximately 5% the original moisture contentand stored. Before testing, the sheet stock was hydrated to 118-122% itsstorage weight and then cut into 0.7 cm discs which were placed on thesurface of saline agar plates. The plates were incubated for 24 hours at4° C. and then developed by the addition of 0.25M HCl solution whichcauses proteins to precipitate. Zones of protein precipitate weremeasured only around the discs that had protein incorporated into thematrix, indicating the release of active protein after its incorporationinto the matrix.

EXAMPLE 11 Interleukin-2 Incorporation into and Delivery from the Matrix

The growth factor interleukin-2 was incorporated into polymerized matrixmaterial by soaking re-hydrated plain stock sheet in fluid containingthe growth factor. After 24 hours of soaking at 4° C., the matrix pieceswere cut into one cm circles and placed into saline. Samples of theelution fluid were taken at intervals and assayed by ELISA (EnzymeLinked Immunosorbent Assay) for interleukin-2 to determine if materialentered the matrix and was then released. The results showed thatproportionately more IL-2 was eluted from the matrix over time.

EXAMPLE 12 Temporal Release of Antifungal Agent

Fluconazole was incorporated by the addition of the active agent to apre-polymerized batch of matrix. After polymerization, dehydration andrehydration, a disc containing the active agent was placed onto an agarplate for two hours at 4° C. Thereafter, every two hours for a total of154 hours, the disc was removed and transferred to a new spot on thesurface of the agar. After all transfers had been carried out, theplates were inoculated with Candida albicans and incubated at 35° C.until confluent growth had occurred. The serial transfer spots on theplates were then examined for zones of inhibition. The results showedthat the device delivered a high dose of fluconazole in the first eighthours and then a steady concentration thereafter until the 140th hourwhen the concentration, according to zone size, began to diminish.

EXAMPLE 13 Delivery of a Biologically Functional Protein from the Matrix

Human transferrin is an iron chelating protein of approximately 70,000MW. Transferrin was incorporated into the pre-polymerized batch mix at0.05% w/w, mixed, and then encapsulated by polymerization with TEMED andammonium persulphate. After dehydration, rehydration and cutting, discsof 0.7 cm were placed onto the surface of nutrient agar plates andincubated at 4° C. for 24 hours. The discs were then removed and theplates were inoculated with Staph aureus and then incubated at 37° C.overnight. The plates were examined for zones of inhibition where thetransferrin removed the trace element iron from the nutrient. Humantransferrin retained its biological activity during incorporation,processing and testing as measured by the zones of inhibition around thespots where transferrin-containing discs had been placed.

It should be understood that the foregoing relates only to preferredembodiments of the present invention and that numerous modifications oralterations may be made therein without departing from the spirit andthe scope of the invention as set forth in the appended claims.

What is claimed is:
 1. A wound dressing device, comprising abiocompatible matrix comprising a polymer network and a non-gellablepolysaccharide, wherein the matrix is configured into multiple strands;wherein a portion of each strand is secured at a common region; andwherein at least one end of each strand is free floating, and having oneor more active agents directly incorporated therein.
 2. The device ofclaim 1, wherein the non-gellable polysaccharide is a non-gellablegalactomannan selected from the group consisting of guar gum, honeylocust bean gum, white clover bean gum, and carob locust bean gum. 3.The device of claim 1, wherein the non-gellable galactomannan is guargum.
 4. The device of claim 1, wherein the polymer is polyacrylamide. 5.The device of claim 1 further comprising a water loss control agent, aplasticizer, and a hydration control agent.
 6. The device of claim 1,wherein the active agents comprise a therapeutic agent and an adjuvant.7. The device of claim 1, wherein the active agent is selected from thegroup consisting of antimicrobial agents, antifungal agents, antiviralagents, metals and wound healing agents.
 8. The device of claim 7,wherein the active agent is an antimicrobial agent selected from thegroup consisting of isoniazid, ethambutol, pyrazinamide, streptomycin,clofazimine, rifabutin, fluoroquinolones, ofloxacin, sparfloxacin,rifampin, azithromycin, clarithromycin, dapsone, tetracycline,erythromycin, ciprofloxacin, doxycycline, ampicillin, amphotericin B,ketoconazole, fluconazole, pyrimethamine, sulfadiazine, clindamycin,lincomycin, pentamidine, atovaquone, paromomycin, diclazaril, acyclovir,trifluorouridine, foscarnet, penicillin, gentamicin, ganciclovir,iatroconazole, miconazole, zinc pyrithione, and silver salts such aschloride, bromide, iodide and periodate.
 9. The device of claim 7,wherein the wound healing agents are selected from the group consistingof growth factors, mucopolysaccharides and proteins.
 10. The device ofclaim 9, wherein the growth factor is selected from the group consistingof fibroblast growth factor (bFGF), acidic fibroblast growth factor(aFGF), nerve growth factor (NGF), epidermal growth factor (EGF),insulin-like growth factors 1 and 2, (IGF-1 and IGF-2), platelet derivedgrowth factor (PDGF), tumor angiogenesis factor (TAF), vascularendothelial growth factor (VEGF), corticotropin releasing factor (CRF),transforming growth factors α and β (TGF-α and TGF-β), interleukin-8(IL-8); granulocyte-macrophage colony stimulating factor (GM-CSF); theinterleukins, and the interferons.
 11. A method for treating wounds,comprising administering a wound healing device comprising abiocompatible matrix comprising a polymer network and a non-gellablepolysaccharide wherein the matrix is configured into multiple strands:wherein a portion of each strand is secured at a common region; andwherein at least one end of each strand is free floating, and having oneor more active agents directly incorporated therein.
 12. The method ofclaim 11, wherein the active agent is selected from the group consistingof antimicrobial agents, antifungal agents, antiviral agents, metals andwound healing agents.
 13. The method of claim 11, wherein the activeagent is selected from the group consisting of antimicrobial agents,antifungal agents, antiviral agents, metals and wound healing agents.14. The method of claim 13, wherein the active agent is an antimicrobialagent selected from the group consisting of isoniazid, ethambutol,pyrazinamide, streptomycin, clofazimine, rifabutin, fluoroquinolones,ofloxacin, sparfloxacin, rifampin, azithromycin, clarithromycin,dapsone, tetracycline, erythromycin, ciprofloxacin, doxycycline,ampicillin, amphotericin B, ketoconazole, fluconazole, pyrimethamine,sulfadiazine, clindamycin, lincomycin, pentamidine, atovaquone,paromomycin, diclazaril, acyclovir, trifluorouridine, foscarnet,penicillin, gentamicin, ganciclovir, iatroconazole, miconazole, zincpyrithione, and silver salts such as chloride, bromide, iodide andperiodate.
 15. The method of claim 13, wherein the wound healing agentsare selected from the group consisting of growth factors,mucopolysaccharides and proteins.
 16. The method of claim 13, whereinthe growth factor is selected from the group consisting of fibroblastgrowth factor (bFGF), acidic fibroblast growth factor (aFGF), nervegrowth factor (NGF), epidermal growth factor (EGF), insulin-like growthfactors 1 and 2, (IGF-1 and IGF-2), platelet derived growth factor(PDGF), tumor angiogenesis factor (TAF), vascular endothelial growthfactor (VEGF), corticotropin releasing factor (CRF), transforming growthfactors α and β (TGF-α and TGF-β), interleukin-8 (IL-8);granulocyte-macrophage colony stimulating factor (GM-CSF); theinterleukins, and the interferons.